CN114105797A - Method for recovering D-p-hydroxyphenylglycine from crystallization mother liquor - Google Patents
Method for recovering D-p-hydroxyphenylglycine from crystallization mother liquor Download PDFInfo
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- CN114105797A CN114105797A CN202111064103.0A CN202111064103A CN114105797A CN 114105797 A CN114105797 A CN 114105797A CN 202111064103 A CN202111064103 A CN 202111064103A CN 114105797 A CN114105797 A CN 114105797A
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- LJCWONGJFPCTTL-SSDOTTSWSA-N D-4-hydroxyphenylglycine Chemical compound [O-]C(=O)[C@H]([NH3+])C1=CC=C(O)C=C1 LJCWONGJFPCTTL-SSDOTTSWSA-N 0.000 title claims abstract description 113
- 238000002425 crystallisation Methods 0.000 title claims abstract description 86
- 230000008025 crystallization Effects 0.000 title claims abstract description 85
- 238000000034 method Methods 0.000 title claims abstract description 75
- 239000012452 mother liquor Substances 0.000 title claims abstract description 75
- 238000001728 nano-filtration Methods 0.000 claims abstract description 67
- 239000007788 liquid Substances 0.000 claims abstract description 32
- 239000000706 filtrate Substances 0.000 claims abstract description 21
- 238000001914 filtration Methods 0.000 claims abstract description 17
- 238000013375 chromatographic separation Methods 0.000 claims abstract description 15
- 239000000919 ceramic Substances 0.000 claims abstract description 14
- 239000000047 product Substances 0.000 claims abstract description 14
- 239000013078 crystal Substances 0.000 claims abstract description 13
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 claims abstract description 12
- 238000005374 membrane filtration Methods 0.000 claims abstract description 9
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 claims abstract description 5
- 235000011114 ammonium hydroxide Nutrition 0.000 claims abstract description 5
- 238000001035 drying Methods 0.000 claims abstract description 5
- 230000008569 process Effects 0.000 claims description 35
- 239000012141 concentrate Substances 0.000 claims description 13
- BFNBIHQBYMNNAN-UHFFFAOYSA-N ammonium sulfate Chemical compound N.N.OS(O)(=O)=O BFNBIHQBYMNNAN-UHFFFAOYSA-N 0.000 claims description 11
- 229910052921 ammonium sulfate Inorganic materials 0.000 claims description 11
- 235000011130 ammonium sulphate Nutrition 0.000 claims description 11
- 238000004065 wastewater treatment Methods 0.000 claims description 9
- 238000000926 separation method Methods 0.000 claims description 6
- 239000011347 resin Substances 0.000 claims description 4
- 229920005989 resin Polymers 0.000 claims description 4
- 238000005265 energy consumption Methods 0.000 abstract description 5
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 abstract description 5
- 239000000243 solution Substances 0.000 description 27
- 238000004519 manufacturing process Methods 0.000 description 10
- 239000012528 membrane Substances 0.000 description 10
- LJCWONGJFPCTTL-ZETCQYMHSA-N L-4-hydroxyphenylglycine Chemical compound OC(=O)[C@@H](N)C1=CC=C(O)C=C1 LJCWONGJFPCTTL-ZETCQYMHSA-N 0.000 description 6
- 238000011084 recovery Methods 0.000 description 5
- 239000002351 wastewater Substances 0.000 description 5
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 4
- 230000007613 environmental effect Effects 0.000 description 4
- 239000000126 substance Substances 0.000 description 4
- 230000000694 effects Effects 0.000 description 3
- 238000005457 optimization Methods 0.000 description 3
- 238000004064 recycling Methods 0.000 description 3
- 239000007787 solid Substances 0.000 description 3
- 150000003863 ammonium salts Chemical class 0.000 description 2
- 238000005516 engineering process Methods 0.000 description 2
- 230000006872 improvement Effects 0.000 description 2
- 238000010979 pH adjustment Methods 0.000 description 2
- 238000002360 preparation method Methods 0.000 description 2
- 239000002994 raw material Substances 0.000 description 2
- 230000009467 reduction Effects 0.000 description 2
- 230000002194 synthesizing effect Effects 0.000 description 2
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 1
- 229930182555 Penicillin Natural products 0.000 description 1
- 150000001413 amino acids Chemical class 0.000 description 1
- LSQZJLSUYDQPKJ-NJBDSQKTSA-N amoxicillin Chemical compound C1([C@@H](N)C(=O)N[C@H]2[C@H]3SC([C@@H](N3C2=O)C(O)=O)(C)C)=CC=C(O)C=C1 LSQZJLSUYDQPKJ-NJBDSQKTSA-N 0.000 description 1
- 229960003022 amoxicillin Drugs 0.000 description 1
- 230000000844 anti-bacterial effect Effects 0.000 description 1
- 239000003443 antiviral agent Substances 0.000 description 1
- 239000008122 artificial sweetener Substances 0.000 description 1
- 235000021311 artificial sweeteners Nutrition 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 239000003782 beta lactam antibiotic agent Substances 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 125000004122 cyclic group Chemical group 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 238000010586 diagram Methods 0.000 description 1
- 238000010790 dilution Methods 0.000 description 1
- 239000012895 dilution Substances 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- 230000008020 evaporation Effects 0.000 description 1
- 239000012847 fine chemical Substances 0.000 description 1
- 150000004676 glycans Chemical class 0.000 description 1
- 239000012535 impurity Substances 0.000 description 1
- 238000009776 industrial production Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- LSQZJLSUYDQPKJ-UHFFFAOYSA-N p-Hydroxyampicillin Natural products O=C1N2C(C(O)=O)C(C)(C)SC2C1NC(=O)C(N)C1=CC=C(O)C=C1 LSQZJLSUYDQPKJ-UHFFFAOYSA-N 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
- 150000002960 penicillins Chemical class 0.000 description 1
- 229920001282 polysaccharide Polymers 0.000 description 1
- 239000005017 polysaccharide Substances 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 230000000717 retained effect Effects 0.000 description 1
- 239000010865 sewage Substances 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 239000002699 waste material Substances 0.000 description 1
- 239000002132 β-lactam antibiotic Substances 0.000 description 1
- 229940124586 β-lactam antibiotics Drugs 0.000 description 1
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C227/00—Preparation of compounds containing amino and carboxyl groups bound to the same carbon skeleton
- C07C227/38—Separation; Purification; Stabilisation; Use of additives
- C07C227/40—Separation; Purification
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C227/00—Preparation of compounds containing amino and carboxyl groups bound to the same carbon skeleton
- C07C227/38—Separation; Purification; Stabilisation; Use of additives
- C07C227/40—Separation; Purification
- C07C227/42—Crystallisation
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
- C07B2200/00—Indexing scheme relating to specific properties of organic compounds
- C07B2200/07—Optical isomers
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- Crystallography & Structural Chemistry (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The invention discloses a method for recovering D-p-hydroxyphenylglycine from crystallization mother liquor, which comprises the following steps: step 1, adjusting the pH value of crystallization mother liquor to 6.5-7 by using ammonia water; step 2, carrying out ceramic membrane filtration on the crystallization mother liquor obtained in the step 1, and separating into a filtration concentrated solution and a filtration clear solution; step 3, carrying out primary nanofiltration concentration on the filtered clear liquid, and separating the filtered clear liquid into primary nanofiltration clear liquid and primary nanofiltration concentrated liquid; step 4, carrying out continuous chromatographic separation on the primary nanofiltration concentrated solution to obtain an extracting solution; step 5, carrying out secondary nanofiltration concentration on the extracting solution, concentrating to saturation, and separating into secondary nanofiltration clear filtrate and secondary nanofiltration concentrated solution; step 6, adjusting the pH value of the second nanofiltration concentrated solution to 4.5-5 by adopting a sulfuric acid solution, and crystallizing at isoelectric points to separate out a D-p-hydroxyphenylglycine crystal; and 7, drying the D-p-hydroxyphenylglycine crystal to obtain a finished product. The method has the advantages of low water consumption, low energy consumption, high yield and high purity.
Description
Technical Field
The invention belongs to the technical field of pharmacy, and particularly relates to a method for recovering D-p-hydroxyphenylglycine from a crystallization mother liquor.
Background
D-p-hydroxyphenylglycine is an important fine chemical product, is an important raw material for synthesizing side chains of beta-lactam antibiotics (such as penicillins, amoxicillin and the like), and is also an important intermediate for synthesizing antibacterial and antiviral drugs and artificial sweeteners. The D-p-hydroxyphenylglycine is mainly prepared by a biological enzymolysis method or a chemical resolution method, and then purified and refined by the back-end processes of isoelectric point crystallization, crystallization mother liquor recovery and the like.
China is a large producing country of D-p-hydroxyphenylglycine, and in recent years, with the increase of environmental protection and improvement of the country, each production enterprise carries out active process optimization so as to improve the productivity, reduce the cost and improve the quality and simultaneously realize more environmental protection. At present, the process optimization of D-p-hydroxyphenylglycine mainly focuses on a biological enzymolysis preparation method and a chemical resolution preparation method. But the optimization of the back-end process is less studied. The back-end process, particularly the recovery of D-p-hydroxyphenylglycine from the crystallization mother liquor, generates a large amount of wastewater, consumes a large amount of energy and chemicals, and has great environmental protection and cost pressure.
In the traditional production process of D-p-hydroxyphenylglycine, HCl is usually used for adjusting the feed liquid to the isoelectric point in the isoelectric point crystallization procedure, so that the obtained crystallization mother liquor mainly contains NH4Cl (concentration: 50g/L) and D-p-hydroxyphenylglycine (concentration: 25 g/L). The process for recovering the crystallization mother liquor in the prior art comprises the following steps: adjusting the pH value of the mother liquor to be neutral (6.6-7) by using ammonia water, and then separating D-p-hydroxyphenylglycine and micromolecule ammonium salt by using a nanofiltration membrane. After the D-p-hydroxyphenylglycine is nanofiltered and concentrated to 250g/L, the D-p-hydroxyphenylglycine is precipitated by using an isoelectric point crystallization method. The crystallization mother liquor recovered in the process is recycled, and the total yield can be increased by 7 percent by repeating the treatment for a plurality of times (generally 7 times). However, the prior art method for recovering D-p-hydroxyphenylglycine from the mother liquor existsThe following defects are caused:
1. the water consumption is high. Repeated recycling of crystallization mother liquor requires repeated dilution, 1m of crystallization mother liquor is treated each time33-4 m of mother liquor needs to be added3The water consumption is high.
2. The energy consumption is high. The nanofiltration membrane filtration with low molecular weight is a production mode with high energy consumption. 1kg of finished product requires 12 kw.h of energy. In addition, a large amount of waste water also needs to be evaporated, and the evaporation cost can reach 1m3The waste water consumed 0.3T of steam (1.2 bar).
3. The quality of the product is reduced. Multiple pH adjustments can result in changes in the chirality of D-p-hydroxyphenylglycine, which is converted to L-p-hydroxyphenylglycine, with the L form having severe toxic side effects.
Disclosure of Invention
The present invention has been made to solve the above problems, and an object of the present invention is to provide a novel method for recovering D-p-hydroxyphenylglycine from a crystallization mother liquor.
In order to achieve the purpose, the invention adopts the following technical scheme:
the invention provides a method for recovering D-p-hydroxyphenylglycine from crystallization mother liquor, which is characterized by comprising the following steps: the crystallization mother liquor adopted by the method is obtained by adjusting the pH to the isoelectric point by using a 20% sulfuric acid solution in the isoelectric point crystallization procedure of the D-p-hydroxyphenylglycine production process, and the method for recovering the D-p-hydroxyphenylglycine from the crystallization mother liquor comprises the following steps: step 1, adjusting the pH value of a crystallization mother liquor to 6.5-7 by using ammonia water; step 2, carrying out ceramic membrane filtration on the crystallization mother liquor obtained after the treatment in the step 1, and separating the crystallization mother liquor into a filtration concentrated solution and a filtration clear solution; step 3, carrying out primary nanofiltration concentration on the filtered clear liquid obtained in the step 2, wherein the concentration multiple is 6 times, separating the filtered clear liquid into primary nanofiltration clear liquid and primary nanofiltration concentrated liquid, and keeping the D-p-hydroxyphenylglycine to be recovered in the primary nanofiltration concentrated liquid; step 4, carrying out continuous chromatographic separation on the first nanofiltration concentrated solution obtained in the step 3 to obtain an extracting solution; step 5, carrying out second nanofiltration concentration on the extracting solution obtained in the step 4, concentrating to saturation, separating into second nanofiltration clear filtrate and second nanofiltration concentrated solution, and keeping D-p-hydroxyphenylglycine to be recovered in the second nanofiltration concentrated solution; step 6, adjusting the pH value of the second nanofiltration concentrated solution obtained in the step 5 to 4.5-5 by adopting a sulfuric acid solution, and carrying out isoelectric point crystallization to separate out a D-p-hydroxyphenylglycine crystal; and 7, drying the D-p-hydroxyphenylglycine crystal to obtain a finished product.
The method for recovering D-p-hydroxyphenylglycine from the crystallization mother liquor provided by the invention also has the following characteristics: wherein the content of D-p-hydroxyphenylglycine in the initial crystallization mother liquor in the step 1 is 2%.
The method for recovering D-p-hydroxyphenylglycine from the crystallization mother liquor provided by the invention also has the following characteristics: wherein the molecular weight cut-off of the ceramic membrane filtration in the step 2 is 15K daltons.
The method for recovering D-p-hydroxyphenylglycine from the crystallization mother liquor provided by the invention also has the following characteristics: wherein, the filtration concentrate in the step 2 returns to the feeding tank for ceramic membrane filtration, and a wastewater treatment process is performed every time the volume of the filtration concentrate reaches 1/200 of the feeding volume; filtering the clear filtrate, and directly entering the next step, wherein the concentration multiple is more than 200 times.
The method for recovering D-p-hydroxyphenylglycine from the crystallization mother liquor provided by the invention also has the following characteristics: wherein the interception molecular weight of the first nanofiltration concentration in the step 3 is 200 daltons, the content of D-p-hydroxyphenylglycine in the first nanofiltration concentrated solution is more than or equal to 12 percent, and the content of D-p-hydroxyphenylglycine in the first nanofiltration clear filtrate is less than or equal to 0.1 percent.
The method for recovering D-p-hydroxyphenylglycine from the crystallization mother liquor provided by the invention also has the following characteristics: wherein the continuous chromatographic separation in the step 4 is carried out at normal temperature, the feeding mode is continuous feeding, the linear speed of the feeding speed is 4-5 m/h, an extracting solution and residual liquid are obtained by separation, the content of D-p-hydroxyphenylglycine in the extracting solution is more than or equal to 6%, and the purity of the D-p-hydroxyphenylglycine is more than or equal to 93%; the content of D-p-hydroxyphenylglycine in the residual liquid is less than or equal to 0.5 percent, and the content of ammonium sulfate is more than or equal to 8 percent.
The method for recovering D-p-hydroxyphenylglycine from the crystallization mother liquor provided by the invention also has the following characteristics: wherein, in the continuous chromatographic separation of the step 4, the resin is selected from any one of XA2004/32K series, XA3114 series and XA5007 series.
The method for recovering D-p-hydroxyphenylglycine from the crystallization mother liquor provided by the invention also has the following characteristics that: and a step of concentrating and crystallizing the obtained residual liquid to extract ammonium sulfate.
The method for recovering D-p-hydroxyphenylglycine from the crystallization mother liquor provided by the invention also has the following characteristics: wherein the molecular weight cut-off of the second nanofiltration concentration is 200 daltons, the content of D-p-hydroxyphenylglycine in the second nanofiltration concentrated solution is more than or equal to 20%, and the purity of D-p-hydroxyphenylglycine is more than or equal to 93%; the content of D-p-hydroxyphenylglycine in the second nanofiltration filtrate is less than or equal to 0.1 percent.
The method for recovering D-p-hydroxyphenylglycine from the crystallization mother liquor provided by the invention also has the following characteristics: wherein, the crystallization mother liquor obtained after D-p-hydroxyphenylglycine crystals are separated out in the step 6 is directly subjected to a wastewater treatment process without being recycled
The invention has the beneficial effects that:
the method for recovering D-p-hydroxyphenylglycine from the crystallization mother liquor disclosed by the invention applies a continuous chromatographic separation technology (SSMB) to replace the traditional process for treating the crystallization mother liquor to recover the D-p-hydroxyphenylglycine, and has the following advantages:
(1) in the process method, the crystallization mother liquor is filtered by a ceramic membrane to remove impurities, then enters a nanofiltration membrane system to be concentrated to the feed concentration of the SSMB chromatographic system, and is concentrated by secondary nanofiltration, so that the final total yield can reach 85-90%. In addition, only one crystallization is needed in the steps of the process method, the D-p-hydroxyphenylglycine in the crystallization mother liquor obtained after the crystallization is basically utilized to the utmost extent, and the crystallization mother liquor does not need to be recycled repeatedly. Obviously different from the prior art that the crystallization mother liquor of the crystallization mother liquor needs to be recycled by recycling and repeatedly recovering to improve the total yield. And because the cyclic and repeated recovery of the crystallization mother liquor is avoided, and a large amount of water and energy consumption in repeated procedures are avoided, the water consumption required by only one process is extremely low, and the energy consumption is also low. The invention obviously reduces the sewage discharge and accords with the environmental protection trends of clean production and waste reduction.
(2) The process method does not have the problem of repeated recycling of the crystallization mother liquor for multiple times of circulating treatment, has mild operating conditions, and can effectively avoid the change of the chiral structure of the D-p-hydroxyphenylglycine caused by repeated pH adjustment in the prior art. The recovered D-p-hydroxyphenylglycine has high purity and good product quality.
(3) The process method mainly adopts a continuous chromatographic separation technology, has the characteristics of high productivity and continuous operation, and can reduce the production cost of the D-p-hydroxyphenylglycine.
(4) The crystallization mother liquor adopted in the process method adopts H in the front-end working procedure of recovery2SO4The crystallization mother liquor obtained by isoelectric point crystallization instead of HCl can effectively avoid the influence of high-concentration chloride ions on the SSMB chromatographic equipment and protect the SSMB chromatographic equipment. And before the feed liquid enters the continuous chromatographic separation step, the D-p-hydroxyphenylglycine mother liquor is pretreated by combining a ceramic membrane with a nanofiltration membrane for filtration, so that the problems of resin damage, separation efficiency reduction and the like of SSMB chromatographic equipment during continuous operation of industrial production are prevented. The process method ensures continuous and efficient production of the whole recovery process, provides guarantee for industrial application, and can be popularized and used as an industrial method.
Drawings
FIG. 1 is a process flow diagram of a method for recovering D-p-hydroxyphenylglycine from a crystallization mother liquor in an example of the present invention.
Detailed Description
In order to make the technical means, the creation characteristics, the achievement purposes and the effects of the invention easy to understand, the method for recovering the D-p-hydroxyphenylglycine from the crystallization mother liquor of the invention is specifically described below with reference to the attached drawings.
The invention discloses a method for recovering D-p-hydroxyphenylglycine from crystallization mother liquor. The crystallization mother liquor adopted by the invention is different from the crystallization mother liquor obtained by the traditional production process. In the traditional D-p-hydroxyphenylglycine production process, HCl is used for adjusting feed liquid to an isoelectric point, and then crystallization is carried out, wherein crystallization mother liquor obtained by the process contains chloride ions. The invention adopts the following steps: in the isoelectric point crystallization step, a 20% sulfuric acid solution is used to replace HCl to adjust the pH to the isoelectric point, other process conditions are not changed, and finally obtained crystallization mother liquor (containing no chloride ions) is used as the initial raw material of the method. The crystallization mother liquor which does not contain chloride ions and is adopted by the invention does not have intolerance influence on continuous chromatographic separation equipment.
Referring to fig. 1, the method for recovering D-p-hydroxyphenylglycine from the crystallization mother liquor according to the present invention comprises the following steps:
step 1: adjusting the pH value
The content of D-p-hydroxyphenylglycine (D-HPG) in the crystallization mother liquor adopted in the step is 2 percent, and the pH value is 4.5-5. The content of the substance in the present invention means a mass concentration (hereinafter, the same definition, which will not be described further), and the content of D-HPG 2% means a mass concentration of D-HPG of 2g/100 mL.
Adjusting the pH value of the crystallization mother liquor to 6.5-7 by using ammonia water.
The purpose of this step is to increase the solubility of D-p-hydroxyphenylglycine by changing the pH value.
Step 2: ceramic membrane filtration
And (3) filtering the crystallization mother liquor obtained after the treatment in the step (1) by using a ceramic membrane, wherein the molecular weight cutoff is 15K daltons. Separating the filtrate into a filtrate concentrate and a filtrate after the filtration by the ceramic membrane, and returning the filtrate concentrate to a feeding tank for the filtration by the ceramic membrane; and filtering the filtrate to enter the next step, wherein the concentration multiple is more than 200 times, and the concentration multiple is equal to the volume of the feed volume/the volume of the filtered concentrate. This step is a batch operation, and a wastewater treatment process is performed each time the volume of the filtered concentrate reaches 1/200 of the feed volume. The content of D-p-hydroxyphenylglycine in the filtrate concentrate is 2%, and the pH value is 6.5-7; the content of D-p-hydroxyphenylglycine in the filtered clear liquid is 2 percent, and the pH value is 6.5-7.
The wastewater treatment process in the step is the conventional wastewater environment-friendly treatment process, namely, the wastewater is treated to meet the standard of being discharged into the environment.
The aim of the step is to remove protein and other solid particles through a ceramic membrane so as to protect an organic nanofiltration membrane in the subsequent process.
And step 3: first nanofiltration concentration
And (3) carrying out primary nanofiltration concentration on the filtered clear liquid obtained in the step (2), wherein the molecular weight cutoff is 200 daltons, the concentration multiple is 6 times, and the concentration of the feed liquid reaches 20 Brix. The first nanofiltration concentration is separated into a first nanofiltration filtrate and a first nanofiltration concentrate. D-p-hydroxyphenylglycine to be recovered in the step is remained in the first nanofiltration concentrated solution, and a part of ammonium sulfate enters the first nanofiltration filtrate. The content of D-p-hydroxyphenylglycine in the first nanofiltration concentrated solution is more than or equal to 12 percent, and the pH value is 6.5-7. The content of D-p-hydroxyphenylglycine in the first nanofiltration filtrate is less than or equal to 0.1 percent, and the pH value is 6.5-7. Directly carrying out wastewater treatment on the primary nanofiltration filtrate.
The purpose of this step is to concentrate D-p-hydroxyphenylglycine to 6-fold within the limit of solubility, so that most of D-p-hydroxyphenylglycine remains in the first nanofiltration concentrate, and the concentration and purity of the treated D-p-hydroxyphenylglycine in the solid matter are improved.
And 4, step 4: continuous chromatographic separation
And (3) carrying out continuous chromatographic separation on the first nanofiltration concentrated solution obtained in the step (3), wherein the continuous chromatographic separation is carried out at normal temperature, the feeding mode is continuous feeding, the linear velocity of the feeding speed is 4-5 m/h, and an extracting solution and residual liquid are obtained through separation. In the continuous chromatographic separation of the step, XA2004/32K series for separating organic acid or XA3114 series for separating amino acid can be selected as resin, or XA5007 series for separating polysaccharide can be selected in consideration of the difference of molecular weight between D-p-hydroxyphenylglycine and ammonium salt. Among them, XA2004/32K series showed the best separation effect.
The main component of the extracting solution obtained by the separation in the step is D-p-hydroxyphenylglycine, the content of the D-p-hydroxyphenylglycine is more than or equal to 6 percent, the purity of the D-p-hydroxyphenylglycine is more than or equal to 93 percent, and the pH value is 6.5-7. The detection standard of the invention for the purity is as follows: firstly, the content of D-p-hydroxyphenylglycine is determined by HG/T5804-2021, and then the percentage of the D-p-hydroxyphenylglycine in the solid content of the extracting solution is calculated, namely the purity. The main component of the residual liquid is ammonium sulfate, the content of D-p-hydroxyphenylglycine in the residual liquid is less than or equal to 0.5 percent, the pH value is 6.5 to 7, and the content of ammonium sulfate is more than or equal to 8 percent. Concentrating and crystallizing the obtained residual liquid, and recovering and extracting ammonium sulfate crystals. The process for extracting the ammonium sulfate crystal by concentration crystallization is the conventional process for extracting the ammonium sulfate by concentration crystallization.
And 5: second nanofiltration concentration
And (4) carrying out secondary nanofiltration concentration on the extracting solution obtained in the step (4), concentrating until the molecular weight cut-off is 200 daltons, and separating into a secondary nanofiltration clear liquid and a secondary nanofiltration concentrated solution. D-p-hydroxyphenylglycine to be recovered is retained in the second nanofiltration concentrated solution, the content of the D-p-hydroxyphenylglycine in the second nanofiltration concentrated solution is more than or equal to 20 percent, the purity of the D-p-hydroxyphenylglycine is more than or equal to 93 percent, and the pH value is 6.5-7. The content of D-p-hydroxyphenylglycine in the second nanofiltration filtrate is less than or equal to 0.1 percent, and the pH value is 6.5-7. And directly carrying out wastewater treatment on the second nanofiltration filtrate.
The purpose of this step is to concentrate the feed liquid to saturation, also further remove the residual ammonium sulfate, improve the purity of D-p-hydroxyphenylglycine.
Step 6: isoelectric point crystallization
And (3) adjusting the pH value of the secondary nanofiltration concentrated solution obtained in the step (5) to 4.5-5 by adopting a 20% sulfuric acid solution, performing isoelectric point crystallization, and separating out D-p-hydroxyphenylglycine crystals, wherein the yield reaches 85% -90%, and is the percentage of the total amount of D-p-hydroxyphenylglycine in a dried finished product to the total amount of D-p-hydroxyphenylglycine in the initial crystallization mother liquor. The purity of the dried D-p-hydroxyphenylglycine finished product is not less than 97.5 percent. The content of L-p-hydroxyphenylglycine in the D-p-hydroxyphenylglycine in the dried finished product is very little. The content of L-p-hydroxyphenylglycine in the dried finished product is detected by the method specified in HG/T5804-2021, the content of L-p-hydroxyphenylglycine in the dried finished product is detected, and 15 batches are detected, wherein the content of L-p-hydroxyphenylglycine in 13 batches is not more than 0.05 percent, and the content of L-p-hydroxyphenylglycine in 2 batches is not more than 0.1 percent.
The crystallization mother liquor obtained after D-p-hydroxyphenylglycine crystals are separated out in the step is directly subjected to a wastewater treatment process without being recycled.
Step 7, drying finished product treatment
And drying the D-p-hydroxyphenylglycine crystal to obtain a finished product.
The following table shows the test data obtained by performing three tests of example 1, example 2 and example 3 according to the above steps 1 to 7:
the above embodiments are only specific embodiments of the present invention, and are not intended to limit the scope of the present invention. Any modification, equivalent replacement, or improvement made within the spirit and principle of the present invention shall fall within the protection scope of the present invention.
Claims (10)
1. A method for recovering D-p-hydroxyphenylglycine from crystallization mother liquor is characterized by comprising the following steps:
step 1, adjusting the pH value of a crystallization mother liquor to 6.5-7 by using ammonia water;
step 2, carrying out ceramic membrane filtration on the crystallization mother liquor obtained after the treatment in the step 1, and separating the crystallization mother liquor into a filtration concentrated solution and a filtration clear solution;
step 3, carrying out primary nanofiltration concentration on the filtered clear liquid obtained in the step 2, wherein the concentration multiple is 6 times, separating the filtered clear liquid into primary nanofiltration clear liquid and primary nanofiltration concentrated liquid, and reserving D-p-hydroxyphenylglycine to be recovered in the primary nanofiltration concentrated liquid;
step 4, carrying out continuous chromatographic separation on the first nanofiltration concentrated solution obtained in the step 3 to obtain an extracting solution;
step 5, carrying out second nanofiltration concentration on the extracting solution obtained in the step 4, concentrating to saturation, separating into second nanofiltration clear filtrate and second nanofiltration concentrated solution, and reserving D-p-hydroxyphenylglycine to be recovered in the second nanofiltration concentrated solution;
step 6, adjusting the pH value of the second nanofiltration concentrated solution obtained in the step 5 to 4.5-5 by adopting a sulfuric acid solution, and carrying out isoelectric point crystallization to separate out a D-p-hydroxyphenylglycine crystal;
and 7, drying the D-p-hydroxyphenylglycine crystal to obtain a finished product.
2. The process for recovering D-p-hydroxyphenylglycine from a crystallization mother liquor according to claim 1, characterized in that:
wherein the content of D-p-hydroxyphenylglycine in the initial crystallization mother liquor in the step 1 is 2%.
3. The process for recovering D-p-hydroxyphenylglycine from a crystallization mother liquor according to claim 1, characterized in that:
wherein the molecular weight cut-off of the ceramic membrane filtration in the step 2 is 15K daltons.
4. The process for recovering D-p-hydroxyphenylglycine from a crystallization mother liquor according to claim 1, characterized in that:
wherein, the filtration concentrate in the step 2 returns to the feeding tank for ceramic membrane filtration, and a wastewater treatment process is performed every time the volume of the filtration concentrate reaches 1/200 of the feeding volume; filtering the clear filtrate, and directly entering the next step, wherein the concentration multiple is more than 200 times.
5. The process for recovering D-p-hydroxyphenylglycine from a crystallization mother liquor according to claim 1, characterized in that:
wherein the molecular weight cut-off of the first nanofiltration concentration in the step 3 is 200 daltons,
the content of D-p-hydroxyphenylglycine in the first nanofiltration concentrated solution is more than or equal to 12 percent,
the content of D-p-hydroxyphenylglycine in the first nanofiltration filtrate is less than or equal to 0.1 percent.
6. The process for recovering D-p-hydroxyphenylglycine from a crystallization mother liquor according to claim 1, characterized in that:
wherein the continuous chromatographic separation in the step 4 is carried out at normal temperature, the feeding mode is continuous feeding, the linear velocity of the feeding speed is 4-5 m/h, the extracting solution and the residual liquid are obtained by separation,
the content of the D-p-hydroxyphenylglycine in the extracting solution is more than or equal to 6 percent, and the purity of the D-p-hydroxyphenylglycine is more than or equal to 93 percent;
the content of D-p-hydroxyphenylglycine in the residual liquid is less than or equal to 0.5 percent, and the content of ammonium sulfate is more than or equal to 8 percent.
7. The process for recovering D-p-hydroxyphenylglycine from a crystallization mother liquor according to claim 6, wherein:
wherein, in the continuous chromatographic separation of the step 4, the resin is selected from any one of XA2004/32K series, XA3114 series and XA5007 series.
8. The method for recovering D-p-hydroxyphenylglycine from a crystallization mother liquor according to claim 6, further comprising:
and concentrating and crystallizing the obtained residual liquid to extract ammonium sulfate.
9. The process for recovering D-p-hydroxyphenylglycine from a crystallization mother liquor according to claim 1, characterized in that:
wherein the molecular weight cut-off of the second nanofiltration concentration is 200 daltons,
the content of D-p-hydroxyphenylglycine in the second nanofiltration concentrated solution is more than or equal to 20 percent, and the purity of D-p-hydroxyphenylglycine is more than or equal to 93 percent;
the content of D-p-hydroxyphenylglycine in the second nanofiltration filtrate is less than or equal to 0.1 percent.
10. The process for recovering D-p-hydroxyphenylglycine from a crystallization mother liquor according to claim 1, characterized in that:
wherein, the crystallization mother liquor obtained after D-p-hydroxyphenylglycine crystals are separated out in the step 6 is directly subjected to a wastewater treatment process without being recycled.
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN116120343A (en) * | 2023-02-06 | 2023-05-16 | 艾美科健（中国）生物医药有限公司 | Method for extracting raw material mother nucleus 7-APRA and side chain D-HPG from cefprozil raw material drug waste liquid synthesized by enzyme method |
Citations (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1997045185A1 (en) * | 1996-05-24 | 1997-12-04 | Cultor Ltd. | Method for fractionation of a solution by a chromatographic simulated moving bed process |
| CN102392060A (en) * | 2011-09-16 | 2012-03-28 | 石药集团中润制药(内蒙古)有限公司 | Recovering method of effective components in amoxicillin enzymatic synthesis mother liquor by utilizing nanofiltration |
| CN102851332A (en) * | 2012-09-07 | 2013-01-02 | 石药集团中诺药业（石家庄）有限公司 | Recovery method for D(-)phenylglycine in ampicillin mother liquid by using enzyme method |
| CN103483213A (en) * | 2013-08-26 | 2014-01-01 | 厦门世达膜科技有限公司 | Method for separating p-hydroxyphenylglycine and ammonium sulfate from glycine mother solution |
| CN104357528A (en) * | 2014-10-29 | 2015-02-18 | 国药集团威奇达药业有限公司 | Method for comprehensively recovering effective ingredients in amoxicillin mother liquid prepared by enzyme process |
| CN105254520A (en) * | 2015-10-12 | 2016-01-20 | 国药集团威奇达药业有限公司 | Recovery method for D-hydroxyphenylglycine in amoxicillin crystallization mother liquor of enzymatic synthesis |
| KR20190139825A (en) * | 2018-01-31 | 2019-12-18 | 씨제이제일제당 (주) | Method for Preparing Natural L-cysteine Crystals by Continuous Chromatography |
| CN111393315A (en) * | 2020-02-20 | 2020-07-10 | 国药集团威奇达药业有限公司 | Method for recovering D-p-hydroxyphenylglycine in D-p-hydroxyphenylglycine crystallization mother liquor synthesized by enzyme method |
-
2021
- 2021-09-10 CN CN202111064103.0A patent/CN114105797B/en active Active
Patent Citations (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1997045185A1 (en) * | 1996-05-24 | 1997-12-04 | Cultor Ltd. | Method for fractionation of a solution by a chromatographic simulated moving bed process |
| CN102392060A (en) * | 2011-09-16 | 2012-03-28 | 石药集团中润制药(内蒙古)有限公司 | Recovering method of effective components in amoxicillin enzymatic synthesis mother liquor by utilizing nanofiltration |
| CN102851332A (en) * | 2012-09-07 | 2013-01-02 | 石药集团中诺药业（石家庄）有限公司 | Recovery method for D(-)phenylglycine in ampicillin mother liquid by using enzyme method |
| CN103483213A (en) * | 2013-08-26 | 2014-01-01 | 厦门世达膜科技有限公司 | Method for separating p-hydroxyphenylglycine and ammonium sulfate from glycine mother solution |
| CN104357528A (en) * | 2014-10-29 | 2015-02-18 | 国药集团威奇达药业有限公司 | Method for comprehensively recovering effective ingredients in amoxicillin mother liquid prepared by enzyme process |
| CN105254520A (en) * | 2015-10-12 | 2016-01-20 | 国药集团威奇达药业有限公司 | Recovery method for D-hydroxyphenylglycine in amoxicillin crystallization mother liquor of enzymatic synthesis |
| KR20190139825A (en) * | 2018-01-31 | 2019-12-18 | 씨제이제일제당 (주) | Method for Preparing Natural L-cysteine Crystals by Continuous Chromatography |
| CN111393315A (en) * | 2020-02-20 | 2020-07-10 | 国药集团威奇达药业有限公司 | Method for recovering D-p-hydroxyphenylglycine in D-p-hydroxyphenylglycine crystallization mother liquor synthesized by enzyme method |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN116120343A (en) * | 2023-02-06 | 2023-05-16 | 艾美科健（中国）生物医药有限公司 | Method for extracting raw material mother nucleus 7-APRA and side chain D-HPG from cefprozil raw material drug waste liquid synthesized by enzyme method |
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